Brave Genius

by Sean B. Carroll

  All of the private and public acclaim was not sufficient to quell Camus’s own doubts. Three days after the announcement, he wrote in his notebook:

  Frightened by what happens to me, what I have not asked for. And to make matters worse, attacks so low they pain my heart …

  No matter what, I must overcome this sort of fear, of incomprehensible panic where this unexpected news has thrown me.

  DESPITE THE PARTIES and requests for interviews, and the need to prepare for the days of ceremonies in Stockholm in December, Camus tried to return to business as usual—responding to pleas for intervention and struggling to write anything.

  On October 23, just one week after the Nobel, Camus marked the one-year anniversary of the start of the Hungarian Revolution by publishing an open letter entitled “The Blood of the Hungarians”—a moving extract from his March 15, 1957, speech at the Salle Wagram. A week later, he exercised some of the prestige endowed by the Nobel and joined forces with Mauriac to draw attention to the ongoing trials of four Hungarian writers, and even made a personal visit to the Hungarian Legation in Paris.

  THE WRITER’S ROLE AND RESPONSIBILITY

  In Stockholm, Camus accepted his Prize from King Gustav VI as “a man almost young, rich only in his doubts and with his work still in progress.” In his speech, he deflected the spotlight away from his writing and toward the plight of writers suffering elsewhere, and to the writer’s role and responsibilities in the world. He asked rhetorically, “With what feelings could I accept this honor at a time when other writers in Europe, among them the very greatest, are condemned to silence, and even at a time when the country of my birth is going through unending misery?”

  Camus admitted that in order to cope with his “too generous fortune” he had to rely on the thing that had supported him throughout his life: “the idea that I have had of my art and of the role of the writer.” Camus then asked to explain to his audience, “in a spirit of gratitude and friendship; as simply as I can, what this idea is.”

  The author of The Rebel and the journalist of the Resistance spoke of the writer’s “two tasks that constitute the greatness of his craft: the service of truth and the service of liberty.” The witness to the Spanish Civil War, World War II, the Cold War, and the Battle of Algiers said: “For more than twenty years of an insane history, hopelessly lost like all the men of my generation in the convulsions of time, I have been supported by one thing: by the hidden feeling that to write today was an honor because this activity was a commitment—and a commitment not only to write” but “to bear, together with all those who were living through the same history, the misery and the hope we shared.”

  For Camus, the writer’s responsibility was to unite the greatest number of people, and not to compromise his art by serving those in power who make history. Rather, the writer was to be at the service of those who suffer under that power, and to make their suffering “resound by means of his art.” Camus asserted, “The nobility of our craft will always be rooted in two commitments, difficult to maintain: the refusal to lie about what one knows and the resistance to oppression.” He concluded by accepting his Prize “as an homage rendered to all those who, sharing in the same fight, have not received any privilege, but have on the contrary known misery and persecution.”

  Four days later, Camus traveled north to the University of Uppsala, where he addressed a rapt audience in the Aula—the grand, ornate auditorium in the main hall of the university. Camus spoke on the subject of “the artist and his time.” His main theme concerned how, in contrast to previous times when the artist could remain aloof on the sidelines in history’s amphitheater, artists and writers in particular were now in the amphitheater. Camus asserted that the era “of the revered master … of the armchair genius is over.” The question facing all artists in such an age was how, “among the police forces of so many ideologies,” to create work of significance.

  After examining all of the forces that had threatened and undermined the freedom and respectability of art in recent decades—the submission to tyranny, comfort-seeking superficiality, an indifferent public—Camus suggested that the very convulsions of the times would lead to a rebirth of great art. His conclusion was in many ways an autobiographical statement:

  Let us rejoice … at having witnessed the death of a lying and comfort-loving Europe and at being faced with cruel truths. Let us rejoice … because a prolonged hoax has collapsed and we see clearly what threatens us. And let us rejoice as artists, torn from our sleep and our deafness, forced to keep our eyes on destitution, prisons, and bloodshed. If, faced with such a vision, we can preserve the memory of days and of faces, and if, conversely, faced with the world’s beauty, we manage not to forget the humiliated, then Western art will gradually recover its strength and its sovereignty … Danger makes men classical and all greatness, after all, is rooted in risk.

  CHAPTER 28

  THE LOGIC OF LIFE

  In formal logic, a contradiction is the signal of a defeat, but in the evolution of real knowledge it marks the first step in progress towards a victory.

  —ALFRED NORTH WHITEHEAD (1861–1947),

  Science and the Modern World

  AS CAMUS WAS COPING WITH THE GLARE OF THE NOBEL SPOTLIGHT, Jacob and Monod were taking their first steps together that would lead them, too, to Stockholm.

  The two men had seen each other nearly every day during the first few years that Jacob worked in Lwoff’s group. At the end of 1954, Monod moved out of the attic to the ground floor of the building when he became head of the Department of Cellular Biochemistry, but that did not disrupt their connection. The communal lunches moved to more spacious quarters adjoining Monod’s new laboratory. Although their respective research efforts were independent of one another—Jacob was immersed in the genetics of bacteriophage, Monod in the induction of enzymes in bacteria—the two stayed current with each other’s work.

  By the fall of 1957, Monod realized that if he was going to make further progress in understanding the genetic control of enzyme induction, he needed to apply the latest techniques of genetic analysis. Fortunately for him, the best expert he could have possibly recruited in the world was his former attic mate Jacob.

  Over the previous three years, and working closely with Elie Wollman, Jacob had pioneered ways for mapping genes and mutations on bacterial and bacteriophage chromosomes. The advances were due to completely unforeseen properties of bacterial mating. The two men discovered a phenomenon they dubbed “erotic induction,” in which the mating of a lysogenic “male” with a nonlysogenic “female” led to the induction of the prophage and the lysis of the nonlysogenic strain. Importantly, Jacob and Wollman determined that the mating in the opposite direction, of a non-lysogenic male with a lysogenic female, did not cause induction. The two different results caused them to realize that during erotic induction, the genes of the prophage were being transferred to the recipient, and then being expressed to produce an infectious virus. This notion led Jacob and Wollman to explore how genetic material was transferred from one bacterial cell to another.

  It was Wollman who had the idea of breaking off matings to see when and how genes were transferred. They dubbed it the “coitus interruptus” experiment. Madame Jacob had found no use for the Waring blender that her husband had purchased for her in the States. In fact, she hated it and would not use it, so Jacob stored it in the laboratory in case it might be useful. It turned out to be incredibly handy—as a bacterial contraceptive. Upon whirling the bacteria in the blender at different times after they started mating, Jacob and Wollman were astonished to discover that different genes were transmitted at different, but reproducible, times after mating. One gene was detectable after five minutes, another after ten, another after eighteen, and so forth, up to one hundred minutes to transfer the entire chromosome. It was almost unbelievable that a bacterium that took only twenty minutes to divide would engage in mating for a period five times longer than its life cycle. Of course, the fact that sex could l
ast that long was especially impressive, even to Frenchmen.

  The discovery was a turning point in bacterial genetics, for it gave the entire field a way to map the relative location of genes as a function of the time when they were transferred during mating. Monod referred to the method as the “spaghetti” approach: the chromosome was taken up by a recipient cell like a string of spaghetti, and then the untransferred portion was broken off at specific points in time. Monod needed such expertise to map mutations in genes involved in enzyme induction. He and Jacob decided to join forces.

  It was a pairing of complementary strengths in both scientific expertise and styles. Monod was more quantitative and biochemical, comfortable with enzymes and measurements. Jacob was at home in the more abstract realm of genetics, where the activities of genes were observed indirectly, such as the ability of a bacterium to grow on a plate containing certain nutrients. Monod was a superb and practiced logician who excelled at analyzing all possible interpretations consistent with a set of facts and distilling them into a working theory. Jacob was the more intuitive thinker. Both had demonstrated ingenuity at designing experiments that pushed the boundaries of what had been possible in their respective fields.

  Their intense collaboration would, in just three exceptionally creative years, catapult them to the pinnacle of the new world of molecular biology. And during this momentous and most demanding stretch of his scientific career, Monod would undertake another daring project outside of the lab. In a clandestine operation reminiscent of his days in the Resistance, he would attempt to orchestrate Agnes Ullmann’s and Tamás Erdös’s escape from behind the Iron Curtain.

  BLACK BOXES

  In late 1957, there remained gaping holes in biologists’ general understanding of how genes worked. It was known that genes were located within DNA, but one crucial mystery was how the information in genes was related to the production of proteins—the molecules, like Monod’s enzymes, that did all of the actual work inside cells and bodies.

  The first complete structure of a protein, the cow’s version of the insulin hormone, was only just solved in 1955. That achievement and related efforts demonstrated that proteins were made of chains of twenty different amino acids, and suggested that each of the thousands of different proteins in a cell was comprised of a unique sequence of amino acids. But it was entirely unclear how any one protein, let alone the thousands in a cell, was manufactured, or what role genes and DNA played. Understanding the relationship between genes and proteins was crucial to understanding how genes determined the characteristics of all organisms—their life, their growth, and their physiology.

  In mid-September, Jacob and other biologists broadly concerned with genes and proteins convened for a meeting of the British Society for Experimental Biology at University College, London. At the time, different scientists were working on different models—bacteria, viruses, rat liver, pigeon pancreas—and different proteins, and employing vastly different experimental approaches. As a result, there was a variety of ideas circulating both at the meeting and in the scientific literature about how proteins were manufactured, as well as a great deal of confusion about what had been learned that was particular to the protein, tissue, or species examined, and what might be generally true.

  Then Francis Crick stepped up to the podium.

  The theoretician had helped solve the structure of DNA using a lot of data that had been obtained by others. Now, without having conducted a single experiment himself, he tried to bring some clarity to the issues swirling around genes and the making of proteins.

  In the printed version of his address, “On Protein Synthesis,” Crick argued that “in biology proteins are uniquely important” and “they can do almost anything” because they are responsible for all of the chemical reactions in cells and bodies. He asserted that “the main function of the genetic material [DNA] is to control (not necessarily directly) the synthesis of proteins.” He acknowledged, “There is a little direct evidence to support this, but to my mind the psychological drive behind this hypothesis is at the moment independent of such evidence. Once the central and unique role of proteins is admitted there seems little point in genes doing anything else.”

  Crick reviewed the various bits and pieces of what was known at the time, and managed to boil them down into two concrete principles, which he called the “Sequence Hypothesis” and the “Central Dogma.” He admitted, “The direct evidence for both of them is negligible, but I have found them to be of great help in getting to grips with these very complex problems. I present them here in the hope that others can make similar use of them. Their speculative nature is emphasized by their names. It is an instructive exercise to attempt to build a useful theory without using them. One generally ends in the wilderness.”

  Crick explained that in its simplest form, the Sequence Hypothesis “assumes that the specificity of a piece of nucleic acid is expressed solely by the sequence of its bases, and that this sequence is a (simple) code [emphasis added] for the amino acid sequence of a particular protein.” In other words, the linear strings of just four different bases in DNA was somehow a specific chemical blueprint for assembling the proper amino acids, in order, into the unique chains that made each protein.

  Crick then stated his Central Dogma, which suggested that this “information” in DNA, once it has “passed into protein … it cannot get out again [emphasis in original].” Crick insisted that there was thus a directional flow of information from DNA to protein, but not from protein to DNA or other nucleic acids in the cell.

  In both principles, Crick was asserting that there was a simple and general logic underlying the making of all proteins in all organisms. Exactly what that logic could be was entirely unknown:

  CRICK OFFERED SOME ideas about what might occupy that black box between DNA and protein. There was evidence from a variety of sources that ribonucleic acid (RNA) played a role in protein synthesis, and that protein synthesis took place in particles that would soon be named ribosomes. But the RNA known to be in these particles was uniform, which presented a paradox: In light of the great diversity of proteins made in the cell, how could such uniform particles manufacture different proteins? Crick suggested that there may also be another type of RNA, a “template RNA,” in the particles that carried the information for proteins. He also imagined some kind of molecular “adaptors” that shuttled amino acids to the template so that they could be assembled into proteins according to the information in the template RNA.

  Crick acknowledged that “it is remarkable that one can formulate so many principles such as the Sequence Hypothesis and the Central Dogma, which explain many striking facts and yet for which proof is completely lacking. This gap between theory and experiment is a great stimulus to the imagination.”

  Crick stimulated a number of imaginations that day. Jacob later recalled, “In comparison to the confusion, the mess that was the synthesis of proteins, Crick’s speech was extraordinarily simplifying. He brought things into perspective. He showed where we needed to look for something and where we shouldn’t be looking for anything. And he was very surprising.”

  For those who were not present to hear Crick’s lecture, they would have to wait to learn about his bold ideas by word of mouth, or to read his article when it was published the following year.

  AGNES ULLMANN’S DOCTORAL studies were on the very subject of protein synthesis. She had tried very hard to get to England in time to attend the conference at which Crick presented, but she missed the symposium. Despite all that had happened in the previous year, the Kádár regime was allowing some travel outside of Hungary. Ullmann’s thesis adviser, F. Bruno Straub, had encouraged her to go to London for the meeting. She had applied for a passport, and was amazed to receive it while Tamás was still in prison. She had used her maiden name when she applied, and the authorities apparently did not make the connection to her husband. Ullmann thought, “My God, they are not very efficient.”

  The obstacle in getting to England wa
s not the Hungarian government but the British immigration authorities. “The British were awful,” Ullmann recalled. “They didn’t give me the visa.” Despite the well-known plight of Hungarian intellectuals, Ullmann was stonewalled: “They said that maybe they will give it in two months or three months and so on.” By the time the meeting was starting, she did not have her visa.

  Her boss, Straub, however, did get his visa and made it to the symposium. He presented Ullmann’s work on the synthesis of amylase, an enzyme that breaks down starch and that is produced in the pancreas. Their approach was to develop a cell-free chemical extract of pigeon pancreas that was able to produce the enzyme. The idea was that in such an in vitro system, they could treat the extract in various ways to determine which components were necessary for making the enzyme. For example, when Ullmann treated the extract with ribonuclease, an enzyme that destroyed RNA, enzyme synthesis was abolished. This result was consistent with experiments done by many others who found a similar requirement for RNA in protein synthesis. The shortcomings of Ullmann’s and others’ experiments were pointed out by Crick in his lecture: RNA was found in many places inside cells; the RNA associated with different parts of the cell was produced and destroyed at different rates, and so there was probably more than one type of RNA. Crude experiments such as adding ribonuclease to a pancreatic extract could not resolve what role(s) RNA played in protein synthesis.

  When Straub returned to Budapest and Ullmann asked him the news from the meeting, he reported: “There was nothing new.” He did not mention Crick’s lecture.